Examining the Roles of the Translesion DNA Polymerases in DNA Repair

Becky Xu Hua Fu

Abstract

DNA double-strand breaks (DSBs) will lead to cell death unless repaired by DNA repair pathways.  The major DSB repair pathways are homologous recombination -- utilizing 30 base pairs (bp) of homology -- and non-homologous end-joining, utilizing 0-4 bp of homology.  Microhomology-mediated end-joining (MMEJ) is a recently discovered repair pathway that utilizes 5-25 bp of homology.  This study analyzes the role of non-essential DNA polymerases (Rad30, Rev1, Rev3) in MMEJ repair using a novel assay in the model organism Saccharomyces cerevisiae.  The MMEJ assay contains varying amounts of homology (16, 20 or 25 bp) on either side of an inducible DSB, which contain a 2 bp mismatch within the homology.  Each non-essential DNA polymerase is shown to have statistically significant decreases (ranging from 2- to 500- fold) in DSB repair.  Understanding this phenomenon will help determine the mechanisms underlying repair and potentially its role in human disease.

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